As an emerging tissue/organ manufacturing technique, 3D bioprinting has begun to show great promise in advancing the development of functional tissue/organ replacements. However, the biggest current challenges in 3D bioprinted tissues and organs are to create a highly efficient 3D perfused vascular network, in combination with native cell population recruitment, for adequate host integration. As of yet, there has not been a successful implantable 3D bioprinted vascularized scaffold for tissue or organ regeneration. Thus, the objective of this study is to 3D bioprint a highly innovative 3D perfused smart vascular network within a tissue matrix containing biologically-inspired nanobiomaterials for improved neovascularization and tissue formation. My overall design consists of two levels of biomimetic strategies, including architecture design and nanomaterial for improved vascularization and bone formation: (1) biomimetic 3D bioprinted perfused microvascular network and (2) DNA-based nano bioactive factor/drug delivery system. Specifically, the 3D bioprinted perfused microvascular network will play a key role in the efficient transport of nutrients and promotion of tissue formation. The self- assembling nanomaterial delivery system aims to spatiotemporally co-deliver angiogenic and osteogenic factors as well as hydrophobic stem cell-favorable drugs in a precisely controlled manner in situ. The term smart originates from the shape memory material used for our microvascular network, easily tunable 3D bioprinted micro to macro architecture and spatiotemporal organization of multiple bioactive factors via intelligent self-assembling nanomaterials for sustained vascularized bone function recovery. We expect that this project will have a far-reaching impact on not only clinical bone treatment but also other complex tissue/organ regeneration, as well as physical and life science research, if successful.